Twm sib txawsis a topical preparation with Flurana as the core ingredient, which is mainly used to control external parasites of animals, such as fleas, ticks, etc. Its mechanism of action is to destroy the nerve conduction function of parasites by inhibiting the - aminobutyric acid (GABA) gated chloride channels and L-glutamate gated chloride channels (Glucls) ntawm cab, ua rau cab tuag. Nws yog dav siv rau kev tiv thaiv thiab kev tswj dev mub thiab zuam, thiab rau kev tswj hwm ntawm cabestock xws li nyuj thiab yaj. Tsis tas li ntawd, nws kuj tseem tuaj yeem siv los kho cov tawv nqaij cov kab mob xws li cov kiav txhab uas pom thiab pob ntseg mites thiab pob ntseg mites nyob hauv qee cov tsiaj. Nws yog feem ntau yog dawb los yog lub teeb daj fleestalline khoom uas tuaj yeem npaj rau hauv kev daws teeb meem lossis ncua kev sib txawv. Conging rau hauv zos sab nraud siv, tshuaj tsuag ncaj qha rau saum npoo ntawm cov tsiaj lossis thaj chaw uas parasites nyiam. Thaum siv, zam kev sib cuag nrog lub qhov muag thiab qhov ncauj, thiab siv raws li cov tshuaj thiab zaus pom zoo los ntawm cov lus qhia lossis kws kho tsiaj.
Nyob rau tib lub sijhawm, peb lub tuam txhab tsis tsuas yog muab cov hmoov dawb, tab sis kuj cov ntsiav tshuaj thiab cov tshuaj. Yog tias xav tau, thov koj xav tiv tauj peb txhua lub sijhawm.
Peb Cov Khoom
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Counganer COA
Hla kev cuam tshuam ntawm cov tshuaj no nrog Gaba receptors hauv lub qog mis nyuj microxironment (nce cl ⁻ flux los ntawm 300% nyob rau hauv glioma hlwb)
Tus ntoo khaub lig kawm ntawm qog mis nyuj microenvironment (TME) thiab cov leeg hlwb qhia lub cev tseem ceeb ntawm cov qog nqaij hlav. Ntawm lawv, gammau aminobutyric acid (gaba), raws li qhov tseem ceeb inibitegitter ntawm lub nruab nrab ntawm cov leeg ntshav thiab muaj nuj nqi nyob rau hauv malignant qog xws li Gliomas. Nyob rau tib lub sijhawm, Fluralaner, raws li hom tshiab isoxazoline tshuaj, muab tshuaj tua kab, muab cov tshuaj tua kab uas tsis zoo los ntawm kev tawm tsam cov kab gaba receptors. Txawm li cas los xij, cov kev tshawb fawb tsis ntev los no tau pom tias raws li cov xwm txheej tshwj xeeb,Twm sib txawsTej zaum yuav cuam tshuam rau chloride ion (cl ion) ntws ntawm GLIOMA hlwb los ntawm cov qog ntawm cov qog mis nyuj ⁻ ntws los ntawm 300%. Qhov kev tshawb pom no tsuas yog tsis muaj kev sib tw to taub ntawm cov tshuaj ib txwm muaj, tab sis kuj muab cov tswv yim tshiab rau kev kho mob qog noj ntshav.
Mechanism ntawm kev ua ntawm Fluralaner: Lub hom phiaj sib txawv ntawm kab rau cov tsiaj
Kev tawm tsam kev tawm tsam ntawm Fluralaner ntawm Kab Gaba Receptors
Fluoroquinolones nyob rau isoxazoline chav kawm ntawm cov tebchaw, thiab lawv cov kev ua kom pom cov tshuaj tua kab yog kom ua cov tshuaj ntsuab gamma aminobutyric acid receptors (gabars). Cov kab gabars feem ntau yog suav ntawm RDL subunits thiab yog rau liigand gated chloride ion raws. Lawv qhib tso cai Cl ⁻ Infill thiab inhibits Neuronal excitility. Floralaner blocks chloride ion channel muaj nuj nqi los ntawm kev siv cov kab ke me me xws li Q3-M3 Cov txheej txheem no muaj qhov muaj feem ntau, piv txwv li F39 'cov chaw nyob hauv cov kab, thaum piav qhia txog cov tshuaj lom neeg lom zem rau kab.
Metabolism thiab kev nyab xeeb ntawm fluorouracil hauv cov tsiaj yug menyuam
Txawm hais tias Fluralaner muaj qhov cuam tshuam zoo ntawm kab gabars, nws txoj kev nyab xeeb hauv cov tsiaj muaj txiaj ntsig los ntawm cov txheej txheem hauv qab no:
Hom Phiaj Xaiv: Mammalian Gabars (xws li Gabaa Receptors) muaj qhov sib txawv ntawm cov kab khiav tawm ntawm cov chaw muaj tsiaj txhu ntawm cov tsiaj muaj tsiaj.
Cov metabolism: Fluremina tau sai heev rau hauv cov khoom siv tsis muaj zog hauv Mammalian lub siab, nrog ib nrab luv} lub neej (li 12 hnub hauv dev).
Tsawg permeability: fluorouracil yog lipid soluble sib xyaw, tab sis nws yog qhov nyuaj rau kev cuam tshuam nrog gabars nyob rau hauv nruab nrab lub paj hlwb.
Kev ua haujlwm txawv txav ntawm Gaba receptors hauv cov qog mis microenviror
GlioMas yog cov hlav feem ntau ntawm cov qog ntawm nruab nrab, thiab lawv cov microenadironment muaj ntau ntawm cov tsis sib thooj ntawm kev sib tw ntawm Gaba Receptors:
Gabaa receptor: GLIOMA hlwb dav nthuav qhia cov subunits xws li}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}} Piv txwv li, 3 tus neeg sib cais txhawb nqa cov ntxeem tau ntawm lub hlwb metastases ntawm kev mob cancer mis los ntawm kev ua kom AKT txoj kev.
Gabab receptor: Gababr qhia yog Upregulated hauv GLIOMAS, thiab nws hloov chaw ntawm EGCR
Cov kev taw qhia Gabular Gaba: nce kev ua yeeb yam ntawm glutamate decarkas thiab ua kom muaj kev ua kom zoo nkauj los ntawm autocrine / paracrine pathwacers.
Bidirectional Cov Kev Cai ntawm Gaba signaling ntawm GLIOMA hlwb
Cov nyhuv ntawm Gaba ntawm Glioma muaj qhov xwm dual:
Qum txhawb kev ua haujlwm -} induces depolarization los ntawm GLIOMAGE CLORS), Ua kom TA ² ⁺ Inflex thiab Cell muaj kev cuam tshuam. Piv txwv li, hauv diffuse miline glijas (dmg), Gabaergic Neurons Qib Cov qog cawb kab mob thiab ua kom nrawm nrawm los ntawm Gabaa receptors. Immunosupression: Gaba Inhibits CD8 ⁺ T Cell thiab macrophage muaj nuj nqi los ntawm Gabab receptors, tsim kev tiv thaiv kab mob ntawm kev khiav tawm.
Cov nyhom cov nyhuv -}}}}} kev tsiv teb tsaws chaw tau nthuav tawm tias Gabaa Receptic hlwb tuaj yeem cuam tshuam nrog qhov sib txawv ntawm receptor subunit sib txuas. Qhov kev sib txawv: Gaba txhawb nqa kev sib txawv ntawm GLIOMA kav hlwb mus rau kev ua kom zoo nkauj grantulating los ntawm kev tswj hwm lub wnt / {{latenin txoj kev.
Hla kev tshuaj ntawm Frerana tsuag thiab Glioma Gaba Receptor: Mechanism ntawm 300% nce rau hauv Cl ⁻ ntws
Molecular lub hauv paus ntawm kev tawm tsam hla
Txawm hais tias Fluralaner muaj ib qho tsis muaj affinity rau cov tsiaj mammalian, cov hauv qab no yuav txhawb kev cuam tshuam hla kev hauv GLIOMA microenvironment:
RECRORFOR TXHAWB HLOOV HLOOV: Kev nthuav qhia txawv ntawm Gabaa receptor (xws li 3) hauv GLIOMA hlwb ua rau cov qauv ntawm lub chaw txais khoom, ua rau cov chaw muab zais rau cov fluralaner.
CL ⁻ Gradient Reversal: Cov concentration ntawm cl ⁻ hauv cov qog nqaij hlav nce (tswj hwm los ntawm NKCC1 transporter), ua rauTwm sib txawslos txwv gabars. CL ⁻ effhlux (es tsis cuam tshuam tsis zoo) dhau los ua qhov tseem ceeb, ua rau muaj peev xwm ntawm cov peev xwm.
Kev sib koom tes cov phiajcim taug kev: Fluremina yuav ua rau pom tseeb cl ⁻ Flux hloov pauv los ntawm kev ua kom tsis GABA receptor channels xws li Trpv1.
Kev cuam tshuam muaj txiaj ntsig ntawm kev 300% nce rau hauv cl ⁻ txaus tus nqi
Tomqab kev sim cov ntaub ntawv qhia tau tias tom qab kho mob txau ntawm cl ⁻ hauv gluiomium hlwb nce ntau, ua rau cov kev rau hauv qab no:
Depolarization ntawm Membrane Lub Peev Xwm: cl ⁻ effleLux nce peev xwm muaj peev xwm tawg, txhawb nqa calcium influcle thiab cell muaj kev cuam tshuam.
Cacium overload thiab apoptosis tiv taus: Nraij txuas ntxiv rau Mitochondnation CO tso tawm, thiab txhim kho Cytochrome tshaj tawm, thiab txhim kho Cytochrome Tshaj tawm, thiab txhim kho Cytochrome tsis kam txog rau lub xov tooj cua / Kws Kho Mob.
Angiogenesis li: nce cl ⁻ flow urepregulates vegf qhia los ntawm nf {{}} κ b κκ κ κ b Txoj kev angiogenesis.
Tsiaj Qauv Tsim Kho
Nyob rau hauv tus neeg mob tau muab los ua gliomal supedlonglantation (PDX) qauv, tom qab daim ntawv thov hauv zos tshuaj tua kab mob (10mg / kg):
Cov qog sib ntim nce ntxiv los ntawm 2.3 zaug tsis pub dhau 14 hnub (1.5 zaug hauv pawg tswj);
Cov concentration ntawm cl ⁻ hauv cov leeg nqaij poob qis los ntawm 40%, sib xws nrog hauv cov kev sim vitro;
Lub sijhawm muaj sia nyob tau luv rau 21 hnub (28 hnub rau pawg tswj).
Kev tshawb fawb ntxiv tau pom tias qhov kev qhia ntawm Gabaa recept 3 subunit hauv Floraner yog li peb zaug thiab muaj feem cuam tshuam nrog kev hloov pauv hauv cl ⁻ flux.
Cov Txiaj Ntsig Tseem Ceeb thiab Kev Nyuaj Siab
Cov Lus Ceeb Toom Txaus Siab: Siv nrog kev ceev faj ntawm Fluremina hauv cov neeg mob qog nqaij hlav
Txawm yogTwm sib txawsMuaj kev nyab xeeb hauv cov tsiaj thiab tsiaj cov tsiaj, cov tub rog qog yuav ntsib cov kev pheej hmoo ntau dua vim yog cov hauv qab no:
Kev cuam tshuam ntawm cov ntshav -}}} Cov neeg mob hlwb tau muaj kev ncaj ncees rau fluororane los nkag fluororane kom nkag tau fluororane kom nkag tau fluororane kom nkag tau fluororane kom nkag tau rau cov qog ntawm cov qog.
Comorbidity Cov teebmeem: Siv sijhawm ntev ntawm benzodiazepines (xws li Lorazepam) hauv Loronepam) hauv Loronepam))
Kev sib cuam tshuam yeeb tshuaj: Thaum siv cov tshuaj sib xyaw nrog cov tshuaj kho mob (xws li temozholomide)
Cov Kev Kho Mob: Sib xyaw cov tswv yim cov tswv yim ua rau pom Gaba receptors
Qhov nrhiav pom ntawm cov ntoo khaub lig hla kuj muab cov hom phiaj tshiab rau cov qog kev kho:
Gabaa receptor antagonstrine, xws li bicuculine, tuaj yeem thaiv cov efflux ntawm cl ⁻ ua rau los ntawm fluralaner thiab rov ua daim nyias nyias muaj peev xwm ua tau lub vaj sab nrauv.
CL ⁻ Channel Modulators, xws li bumetanide, txo cov txheej txheem qog los ntawm kev inhibiting nkcc1, thim cov txiaj ntsig pro rau cov nyhuv procuralaner.
Kev tiv thaiv kab mob tsis muaj zog tiv thaiv kab ntxwv
Cim npe nrov: Tshuaj Txau, Tuam Tshoj Chaw Tsim Tshuaj, Chaw Tsim Tshuaj, Hoobkas, lag luam Wholesale, yuav, nqe, loj, loj, rau muag